The role of immune cytokines in determining the outcome of intracellular infection has become more evident. In mice, Toxoplasma gondii infection stimulates the production of IFN-xcex3, which is the principal mediator of protection against acute and chronic recrudescent infection. Of the ILs studied, IL-12 appears to be an essential cytokine for stimulating a protective host response (Gazzinelli et al., 1994 J. Immunol., 153:2533; Khan et al., 1994 Infec. Immun., 62:1639; Hunter et al., 1995 Immunology, 84:16). It has been reported that administration of exogenous IL-12 to immunocompetent or SCID mice (Gazzinelli et al., 1993 Proc. Natl. Acad. Sci. USA, 90:6115) protects against subsequent parasite challenge. Both macrophages and CD4+ T cells produce IL-12 that, in turn, stimulates the proliferation of NK cells and CD8+ cytotoxic T cells (Seder et al., 1993 Proc. Natl. Acad. Sci. USA, 90:10188). The role of IL-2 in host protective immunity to Toxoplasma infection is less clear. In mice, administration of exogenous IL-2 can protect against parasite challenge (Sharma et al., 1985 J. Immunol.) 155:4798. The mechanism for this partial protection may be due to an increase in the proliferation of NK cells. It was recently reported that IL-7 can protect against acute Toxoplasma infection (Kasper et al., 1995 J. Immunol., 155:4798). Protection is most evident when IL-7 is administered early and continued throughout the course of infection. The principal T cell subset that mediates protection by IL-7 consists of CD8+ cells. In vitro, these T cells produce IFN-xcex3 and exhibit enhanced TL activity against macrophages infected with T. gondii. 
IL-15 is a recently identified cytokine that is abundantly expressed by a wide variety of tissues and activated monocyte/macrophages (Grabstein et al., 1994 Science, 264:965). The gene for this cytokine has now been isolated from simian kidney epithelial cells (Grabstein, supra). Although the sequence of IL-15 is not homologous with that of IL-2, IL-15 uses components of the IL-2R for bonding and signal transduction (Carson et al., 1994 J. Exp. Med., 180:1395). IL-15 is also a potent growth factor for activated T cells, and it enhances the cytolytic function of both NK and effector T cells. IL-15 appears to enhance LAK cell activity against certain tumors (Gamero et al., 1995 Cancer Res., 55:4988). Although limited information is available on the role of IL-15 in response to infection, recent studies indicate that it stimulates the proliferation it T cells induced by Salmonella infection (Nishimura et al., 1996 J. Immunol., 156:663) and may have a role in the host response to HIV infection (Seder et al., 1995 J. Exp. Med., 182:1067). Endogenous production of IL-15 has now been observed to be important for optimal production of IFN-xcex3 T by NK cells in vitro (Carson et al., 1995 J. Clin. Invest., 96:2578).
It has now been found that mice immunized with Toxoplasma gondii soluble parasite Ag (TLA) and exogenous rIL-15 are protected against lethal Toxoplasma infection. Immunization increases the production IFN-xcex3 and Ag-specific CD8+ T cell proliferation. Adoptive transfer of these CD8+ T cells into a naive host are protective against a lethal T. gondii challenge.
Cytokines of the Th1 profile are important mediators of protective host immunity against Toxoplasma gondii infection in mice. It has now been found that administration of exogenous rIL-15 with soluble Toxoplasma lysate Ag (TLA) provides complete protection against a lethal parasite challenge, whereas treatment with either rIL-15 or TLA alone is not protective. Following immunization with TLA/rIL-15, there is a significant proliferation of splenocytes expressing the CD8+ phenotype in response to TLA. A significant rise in the level of serum IFNxcex3 was observed in vaccinated mice. Adoptive transfer of CD8+ T cells, but not CD4+ T cells, from TLA/rIL-15-vaccinated mice protects naive mice from a lethal parasite challenge. These CD8+ T cells exhibit enhanced CTL activity against target macrophages infected with T. gondii. Mice that have been immunized are protected against lethal parasite challenge for at least 1 month postvaccination. These results demonstrate that TLA when administered with exogenous rIL-15 generates toxoplasmacidal Ag-specific CD8+ cells. These T cells proliferate upon exposure to parasite Ag, exhibit long term memory CTL against infected target cells, and may be involved in host immune memory to this parasite. Accordingly, a novel method of augmenting T cell-mediated immunity against Toxoplasma gondii is provided.